Pediatric Nephrology

, Volume 20, Issue 8, pp 1151–1155

White-coat and masked hypertension in children: association with target-organ damage

Authors

    • Second Department of Pediatrics“P. and A. Kyriakou” Children’s Hospital, National and Kapodestrial University of Athens
  • Vasilios Kotsis
    • Department of Clinical TherapeuticsAlexandra Hospital, National and Kapodestrial University of Athens
  • Savvas Toumanidis
    • Department of Clinical TherapeuticsAlexandra Hospital, National and Kapodestrial University of Athens
  • Christos Papamichael
    • Department of Clinical TherapeuticsAlexandra Hospital, National and Kapodestrial University of Athens
  • Andreas Constantopoulos
    • Second Department of Pediatrics“P. and A. Kyriakou” Children’s Hospital, National and Kapodestrial University of Athens
  • Nikos Zakopoulos
    • Department of Clinical TherapeuticsAlexandra Hospital, National and Kapodestrial University of Athens
Original Article

DOI: 10.1007/s00467-005-1979-5

Cite this article as:
Stabouli, S., Kotsis, V., Toumanidis, S. et al. Pediatr Nephrol (2005) 20: 1151. doi:10.1007/s00467-005-1979-5

Abstract

White-coat hypertension (WCH) and masked hypertension have been associated with increased cardiovascular risk in adults. In the current study, we investigated: (a) the prevalence of WCH and masked hypertension in pediatric patients and (b) the association of these conditions with target organ damage. A total of 85 children underwent office blood pressure measurements, 24-h ambulatory blood pressure monitoring, echocardiography and ultrasonography of the carotid arteries. Subjects with both office and ambulatory normotension or hypertension were characterized as confirmed normotensives or hypertensives, respectively; WCH was defined as office hypertension with ambulatory normotension and masked hypertension as office normotension and ambulatory hypertension. WCH was found in 12.9% and masked hypertension in 9.4% of the subjects. WCH was significantly more prevalent in obese subjects, while masked hypertension was only present in non-obese ones. Confirmed and masked hypertensives had significantly higher left ventricular mass index than confirmed normotensives (34.0±5.8 g/m2.7, 31.9±2.9 g/m2.7 and 25.3±5.6 g/m2.7, respectively, P<0.05). White-coat hypertensives tended to have higher left ventricular mass index than confirmed normotensives, but the difference was not statistically significant (27.8±5.1 g/m2.7 versus 25.3±5.6 g/m2.7). No significant differences were found in the intima-media thickness of the carotid arteries between confirmed normotensives, white-coat hypertensives, masked hypertensives and confirmed hypertensives. WCH and masked hypertension are common conditions in children. Confirmed and masked hypertension in pediatric patients are accompanied by increased left ventricular mass index.

Keywords

Ambulatory blood pressure monitoringWhite-coat hypertensionWhite-coat effectMasked hypertensionTarget-organ damage

Introduction

The prevalence of hypertension in children and adolescents is rising in association with the increasing rates of childhood obesity, and it is associated with early target-organ damage [1]. Published guidelines on high blood pressure in children and adolescents, focused on the early and accurate diagnosis of hypertension, resulted in improved ability to identify children with hypertension [2, 3]. Although auscultation using a mercury sphygmomanometer remains the method of choice for evaluation of hypertension in children, accumulating evidence suggests that ambulatory blood pressure monitoring (ABPM) is a more accurate method for diagnosis, and it is more closely associated with target-organ damage [4, 5]. In addition, ABPM is emerging as a valuable tool in the assessment of white-coat hypertension (WCH), white-coat effect (WCE) and masked hypertension in children [6].

WCH is a condition characterized by a persistently elevated office blood pressure and a persistently normal daytime ambulatory blood pressure. WCE is the difference between clinic systolic blood pressure and mean daytime ambulatory systolic blood pressure. These conditions have been well documented in adults and have been reported to have the same frequency in pediatric patients [6, 7]. Moreover, few clinical trials have evaluated the opposite phenomenon, office normotension with ambulatory blood pressure hypertension, usually called masked hypertension or isolated ambulatory hypertension [8]. In adults, masked hypertension is associated with a similar risk of target-organ damage as in established hypertension [9, 10].

The purpose of the present study was to assess the prevalence of WCH and masked hypertension in children referred to our hypertension center for evaluation of suspected hypertension and the relationship of these conditions to age, gender and obesity. In addition, possible associations between WCH, masked hypertension and target-organ damage were investigated.

Materials and methods

Study population

The study population consisted of 85 consecutive children who were referred to our hypertension center for evaluation of suspected hypertension from their primary health care providers. They had never been previously treated with antihypertensive or lipid-lowering medication. Additional inclusion criteria were no concurrent use of medications affecting blood pressure or secondary causes of hypertension. We excluded secondary hypertension following a standardized diagnostic evaluation that included physical examination, appropriate laboratory tests and diagnostic imaging techniques. Subjects’ body weights were measured with the subjects in light clothing without shoes. Body mass index (BMI) was calculated as weight (kg)/height2 (m2). BMI percentile was determined for each subject according to the 2000 Centers for Disease Control and Prevention growth charts [11]. Obesity was defined as BMI greater than or equal to the 95th percentile for age and gender. All subjects underwent 24-h ABPM, echocardiography and ultrasonography of the carotid arteries. Written consent to participate in the study was obtained from the older children and from both parents of all children. The institutional review board approved the human research protocol.

Office blood pressure measurements

Office blood pressures were measured three times in each subject, at least 1 min apart after 5 min of rest, using a mercury sphygmomanometer (appropriate size cuff [3] applied around the non-dominant arm and systolic and diastolic values identified from the first and fifth phase of Korotkoff sounds). During the measurements, the participant remained seated with the arm comfortably placed at heart level. The same doctor obtained all sphygmomanometric measurements. The criteria indicated by the Fourth Report on the diagnosis, evaluation and treatment of high blood in children and adolescents were used to define office hypertension [2].

Ambulatory blood pressure monitoring

All subjects underwent 24-h ABPM on a usual school day. Subjects did not have physical education during the ABPM day. The Spacelabs 90217 ambulatory blood pressure monitor (Spacelabs Inc., Redmond, WA) was used. The appropriate size cuff was placed around the non-dominant arm, and three blood pressure determinations were made, along with sphygmomanometric measurements on the other arm to verify that the average of the two sets of values did not differ by more than 5 mmHg. Readings were obtained automatically at 15-min intervals throughout the 24-h study period. All subjects included in the study had at least three valid readings per hour. The resulting 72–96 pairs of systolic and diastolic blood pressure readings per recording together with the corresponding time of measurements were used to calculate blood pressure derivatives. All subjects were instructed to rest or sleep between 2200 hours and 0600 hours (nighttime) and to maintain their usual activities between 0600 hours and 2200 hours (daytime). The ABPM criteria reported by Wühl et al., defining ambulatory hypertension as mean daytime systolic blood pressure and/or diastolic blood pressure greater than or equal to the 95th percentile for gender and height, were used [12].

Normotensive subjects with both office and ambulatory blood pressure monitoring were characterized as confirmed normotensives. Hypertensive subjects with both office and ambulatory blood pressure monitoring were characterized as confirmed hypertensives. Subjects with office hypertension and ambulatory normotension were characterized as white-coat hypertensives, and subjects with office normotension and ambulatory hypertension were characterized as masked hypertensives.

Echocardiography

All subjects underwent standard two-dimensional M-mode echocardiograms; left ventricle dimensions were measured using the guidelines of the American Society of Echocardiography [13]. Left ventricular mass was calculated according to an anatomically validated formula [14]. Left ventricular mass index was calculated by dividing left ventricular mass by height2.7 to minimize effect of age gender and overweight status [15, 16].

Ultrasonography of carotid arteries

The left and right internal carotid arteries were examined with a high-resolution ultrasound Doppler system (Acuson 128XP, Mountain View, CA), equipped with a 7-MHz linear-array transducer. Subjects were examined in the supine position, with the head turned 45° from the site being scanned. Both carotid arteries were scanned longitudinally to visualize the intima–media thickness (IMT) in the far wall of the artery. The best images of the far wall that could be obtained were used to determine the IMT. Measurements were made on frozen images, magnified to standard size, on-line. The IMT value was defined as the mean of the right and left, calculated from 10 measurements on each side, taken 10 mm from the carotid bifurcation. The lumen/intima leading edge (I-line) to media/adventitia leading edge (M-line) method, which has been previously validated anatomically, was used. The longitudinal B-scan frames were digitized and analyzed using a computerized image analysis by two investigators blinded to the blood pressure recordings. The reproducibility of sonographers’ IMT measurements had previously been reported [17].

Statistical analysis

The SPSS 10.0 (SPSS Inc., Chicago, IL) statistical package was used to analyze the data. Standard descriptive statistics, two-tailed Student’s t-test, one-way analysis of variance, Pearson’s correlation and chi-square test were used where appropriate. Levene’s test for equality of variances was used to test the normal distribution of variables in the subgroups. P<0.05 was considered statistically significant.

Results

Demographic and clinical data for the 85 patients are listed as mean±SD in Table 1. On the basis of the average office blood pressures, 62.3% of the subjects were normotensives, and 37.6% were hypertensives. ABPM results are shown on Table 2.
Table 1

Demographic and office blood pressure data. Data are shown as mean±SD. BMI body mass index, BP blood pressure

Total

Confirmed normotensives

White-coat hypertensives

Masked hypertensives

Confirmed hypertensives

Age (years)

14.02±4.5

14.0±4.6

14.4±4.4

13.6±4.9

14.2±4.1

Gender (male/female)

50/35

26/19

8/3

3/5

13/8

Height (cm)

161.9±19.8

161.8±16.0

163.2±22.7

149.4±17.08

166.1±18.5

BMI (kg/m2)

24.2±6.1

21.1±3.7

30.2±8.9

20.8±3.05

28.7±6.2

BMI percentile (%)

74.3±27.2

60.9±30.5

90.4±9.9

72.2±15.5

94.2±7.9

Clinic systolic BP (mmHg)

122.0±18.9

108.9±10.9

135.7±9.7

111.0±11.4

137.5±8.9

Clinic diastolic BP (mmHg)

78.9±13.9

71.2±10.4

84.2±9.7

72.0±8.3

88.8±11.2

Clinic systolic BP index

0.92±0.12

0.84±0.07

1.04±0.04

0.91±0.05

1.05±0.11

Clinic systolic BP index

0.92±0.14

0.85±0.11

1.01±0.11

0.89±0.11

1.05±0.13

Table 2

Ambulatory blood pressure data. Data are shown as mean±SD. BP blood pressure

Total

Confirmed normotensives

White-coat hypertensives

Masked hypertensives

Confirmed hypertensives

Mean 24-h systolic BP (mmHg)

119.3±11.7

112.9±6.7

118.6±8.7

124.7±10.4

135.7±11.07

SD 24-h systolic BP (mmHg)

12.6±3.1

11.5±2.5

12.8±2.5

12.4±2.3

13.1±3.5

Mean 24-h diastolic BP (mmHg)

67.9±8.6

65.2±6.05

63.9±7.9

73.6±6.5

76.7±12.9

SD 24-h diastolic BP (mmHg)

11.9±2.5

11.2±1.9

11.5±1.2

11.1±1.2

12.9±3.4

Mean 24-h heart rate (beats/min)

80.1±11.2

79.3±11.6

76.7±13.1

83.6±5.3

81.7±11.1

SD 24-h heart rate (beats/min)

14.1±3.2

14.1±3.1

12.3±2.1

14.5±1.8

15.3±2.5

24-h pulse pressure (mmHg)

51.8±9.1

47.6±6.3

54.6±8.5

51.1±13.6

59.04±7.4

Mean daytime systolic BP (mmHg)

123.1±11.5

116.07±6.9

121.7±6.7

129.1±10.1

137.9±10.1

SD daytime systolic BP (mmHg)

11.5±3.0

10.6±2.3

11.4±2.7

11.6±1.9

12.02±4.1

Mean daytime diastolic BP (mmHg)

71.2±8.2

68.6±6.6

67.2±5.9

77.6±6.2

78.6±11.8

SD daytime diastolic BP (mmHg)

11.2±2.5

10.5±1.8

10.8±2.1

10.2±1.7

11.7±3.5

Mean daytime heart rate (beats/min)

84.1±11.3

83.9±11.5

80.4±14.4

88.5±4.9

84.4±11.7

SD daytime heart rate (beats/min)

13.8±3.4

13.5±3.4

12.06±2.1

14.5±2.1

14.8±2.3

Daytime pulse pressure (mmHg)

51.8±9.3

47.4±6.4

54.4±8.8

51.4±13.9

59.3±7.2

Mean nighttime systolic BP (mmHg)

113.9±14.2

107.1±8.2

113.1±14.1

116.6±11.04

132.5±15.4

SD nighttime systolic BP (mmHg)

10.4±3.0

9.5±2.6

10.8±3.2

8.6±3.3

12.1±3.7

Mean nighttime diastolic BP (mmHg)

62.1±11.5

59.1±6.0

58.1±12.8

66.03±7.0

74.4±18.8

SD nighttime diastolic BP (mmHg)

9.3±2.8

8.8±2.4

7.7±2.1

8.4±1.2

11.1±3.2

Mean nighttime heart rate (beats/min)

72.8±12.3

70.9±13.1

70.3±12.1

74.5±6.7

77.6±13.5

SD nighttime heart rate (beats/min)

9.6±3.7

8.8±2.8

8.2±1.8

8.8±2.3

11.7±5.2

Nighttime pulse pressure (mmHg)

51.7±9.3

47.9±6.8

54.9±8.2

50.6±13.3

58.1±8.5

Daytime systolic BP index

0.92±0.09

0.87±0.05

0.90±0.03

1.01±0.05

1.03±0.11

Daytime diastolic BP index

0.86±0.11

0.83±0.08

0.81±0.07

0.94±0.07

0.95±0.10

Confirmed normotension was found in 52.9% of the subjects, while confirmed hypertension was found in 24.7%. The prevalence of WCH was 12.9% in the study population, while 9.4% of the subjects had masked hypertension. There was no significant difference in the prevalence of WCH in relation to gender or age; however, the presence of obesity was a significant variable. Of the subjects, 23 were obese and 62 non-obese. The prevalence of WCH was 9.6% in non-obese children compared with 21.7% in obese subjects (P<0.0001). Masked hypertension was not associated with age and gender, but it was only present in non-obese subjects (Table 3). Statistically significant differences in BMI percentiles were found between confirmed normotensives and both white-coat and confirmed hypertensives (P<0.05 and P<0.001, respectively). Masked hypertensives tended to have higher BMI percentiles than confirmed normotensives, but the difference was not statistically significant (72.2±15.5 versus 60.9±30.5 percentile).
Table 3

White-coat effect, white-coat hypertension and masked hypertension in obese and non-obese subjects

White-coat hypertension (%)

Masked hypertension (%)

White-coat effect (mmHg)

Obese

21.7*

0

5.53±13.9**

Non-obese

9.6

12.9

−6.79±12.9

*P<0.0001

**P<0.006 versus non-obese subjects

A positive correlation was found between WCE and systolic office blood pressure (r=0.79, P<0.000), age (r=0.34, P<0.001). WCE did not differ between male and female subjects. The magnitude of the systolic WCE was significantly higher in office hypertensive subjects than in normotensive ones (5.15±14.66 mmHg versus −9.10±10.76 mmHg, P<0.001). Moreover, WCE was significantly higher in obese subjects than in non-obese ones (P<0.006) (Table 3).

Target-organ damage tended to be greater in groups with higher ambulatory blood pressure (Table 4). Confirmed hypertensive subjects had significantly higher left ventricular mass index than confirmed normotensive ones (P<0.05). Masked hypertensives also had significantly higher left ventricular mass indices than confirmed normotensive ones (P<0.05). No significant differences were found in left ventricular mass index between masked hypertensives and confirmed hypertensive subjects. Although subjects with WCH had higher left ventricular mass indices than confirmed normotensive ones, the difference was not statistically significant. In addition, no statistically significant differences were found in IMT among confirmed normotensive, WCH, masked hypertensive and confirmed hypertensive subjects (Table 4). Finally, there was no association between target-organ damage and WCE (WCE and left ventricular mass index, r=0.11, P=0.52; WCE and mean intima media thickness of right and left internal carotid arteries, r=0.01, P=0.91; WCE and mean intima media thickness of right and left common carotid arteries, r=0.10, P=0.55).
Table 4

Target organ damage in white-coat, masked and confirmed hypertension. Data are shown as mean±standard deviation for each subgroup. MICA mean intima media thickness of right and left internal carotid arteries, MCCA mean intima media thickness of right and left common carotid arteries

Confirmed normotensives

White-coat hypertensives

Masked hypertensives

Confirmed hypertensives

n (%)

45 (52.9)

11 (12.9)

8 (9.4)

21 (24.7)

Left ventricular Mass/height2.7 (g/m2.7)

25.3±5.6

27.8±5.1

31.9±2.9*

34.0±5.8*

MCCA (mm)

0.48±0.1

0.50±0.01

0.51±0.1

0.54±0.01

MICA (mm)

0.46±0.01

0.51±0.01

0.53±0.1

0.55±0.01

*P<0.05 versus confirmed normotensives

Discussion

The clinical significance of WCH and masked hypertension in children lies in a potentially increased risk for cardiovascular events, as suggested in adults [9, 18]. Previous studies have reported the presence of WCH and masked hypertension in children [6, 8, 19]. However, there are limited data about the relationship of these conditions to target-organ damage.

In the current study, we showed the prevalence of WCH and masked hypertension in children referred to our hypertension center. The prevalence of WCH and masked hypertension was found to be 12.9% and 9.4%, respectively. No association existed between these conditions and age or gender. WCH was significantly more prevalent among obese children, while masked hypertension was only present in non-obese children. However, children with masked hypertension tended to have higher BMI percentiles than confirmed normotensive subjects.

Many studies in adults have suggested that WCH is associated with significant target-organ damage, left ventricular hypertrophy and greater IMT and plaque index than normotensives [9, 17, 20, 21, 22]. Gustavsen et al., in a 10-year follow-up study, showed that subjects with WCH have an increased cardiovascular risk compared with normotensive controls [18]. In our study population, children with WCH tended to have higher left ventricular mass indices than confirmed normotensive subjects but lower than confirmed hypertensive subjects, although no statistically significant differences were found between the groups. In addition, children with WCH had greater BMIs than those with confirmed normotension, reflecting the known relationship between obesity and office blood pressure levels [23]. Both these observations suggest that WCH in children may represent an increased risk for cardiovascular morbidity.

Children with masked hypertension had significantly greater left ventricular mass indices than confirmed normotensive subjects. Left ventricular mass indices in children with masked hypertension were similar on average to confirmed hypertensive subjects. These findings are similar to those in adults, suggesting that patients with masked hypertension show more extensive structural cardiac alterations than confirmed normotensives [9, 10, 24].

The current study also investigates the WCE in pediatric patients. WCE was significantly higher in children with office hypertension than normotensive subjects. A second, more important finding is that WCE was significantly greater in obese children than non-obese subjects. This could explain the absence of masked hypertension in our obese group. Since masked hypertension is equivalent to a negative white-coat effect [25], it is reasonable that masked hypertension is less prevalent in obese children.

One possible limitation of our study is selection bias due to the fact that our population is a referral and not a general population sample. However, many of the children who were referred to our clinic had normal office pressures on repeat testing. These children may benefit from ABPM to rule out masked hypertension. Another limitation of this study is that our data do not provide information on whether masked hypertension is a reproducible phenomenon or becomes less frequent with repeated blood pressure measurements at follow-up visits.

The present study showed that WCH and masked hypertension have a noticeable prevalence in pediatric patients. Masked hypertension is accompanied by increased left ventricular mass, suggesting increased cardiovascular risk in these children. ABPM seems to be an effective method for diagnosing these conditions. However, long-term prospective studies are needed to determine if children with WCH and masked hypertension will have increased rates of future cardiovascular events.

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© IPNA 2005